| 
| ||||||||||||||||||
| These Usp18 (or Ubp43)-mutant mice may be useful in studying interferons and their receptors, cellular function, signal transduction, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N10pN1
Generation DefinitionsDonating Investigator Dong-Er Zhang, University of California, San Diego Description
Homozygous Usp18 (or Ubp43) mutant mice on the FVB/N genetic background are viable and fertile, exhibiting none of the severe neurologic disorders that lead to embryonic lethality or early death reported for Ubp43-deficient mice on a C57BL/6 or mixed B6;129 genetic background. In contrast to wildtype mice, thymi from homozygous mice injected with LPS exhibit no protein from the targeted gene. Expression of the lacZ cassette is observed in both heterozygous and homozygous brain tissues. Homozygous mice are hypersensitive to type I interferon (IFN) and undergo apoptosis upon IFN stimulation. Ubp43-deficiency results in enhanced and prolonged STAT1 phosphorylation, DNA binding, and increased induction of hundreds of interferon stimulated genes (ISGs). Homozygous mice exhibit greater resistance to the cytopathic effects caused by a number of viruses (including lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and Sindbis virus (SNV)). Ubp43-deficient cells exhibit high levels of ISG15 modified proteins. These Usp18 (or Ubp43)-mutant mice may be useful in studying interferons and their receptors, cellular function, signal transduction, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway.In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
Development
A targeting vector was designed to replace exons 2-4 of the targeted gene with a lacZ and PGK-neo cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric mice were bred with C57BL/6 to produce mutant mice. Next, these mice were backcrossed to FVB/N inbred mice for at least 10 generations prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (255 strains)
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Usp18tm1Dez/Usp18tm1Dez
involves: 129S1/Sv * 129X1/SvJ
- mortality/aging
- premature death (MGI Ref ID J:78821)
- behavior/neurological phenotype
- circling
- tight circling (MGI Ref ID J:78821)
- convulsive seizures (MGI Ref ID J:78821)
- spinning
- described as rolling (MGI Ref ID J:78821)
- tremors (MGI Ref ID J:78821)
- cardiovascular system phenotype
- intracerebral hemorrhage
- bloody cerebrospinal fluid was noted (MGI Ref ID J:78821)
- nervous system phenotype
- abnormal cerebral cortex morphology
- thinned cerebral cortex (MGI Ref ID J:78821)
- convulsive seizures (MGI Ref ID J:78821)
- enlarged lateral ventricles
- bilateral enlargement of lateral ventricle and third ventricle (MGI Ref ID J:78821)
- enlarged third ventricle
- bilateral enlargement of lateral ventricle and third ventricle (MGI Ref ID J:78821)
- hydroencephaly
- hydroencephaly first appears at postnatal day 14 (MGI Ref ID J:78821)
- intracerebral hemorrhage
- bloody cerebrospinal fluid was noted (MGI Ref ID J:78821)
This mouse can be used to support research in many areas including:
Cancer Research
Growth Factors/Receptors/Cytokines
Cell Biology Research
Signal Transduction
Developmental Biology Research
Perinatal Lethality
Homozygous
Hematological Research
Immunological Defects
Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
genes regulating susceptibility to infectious disease and endotoxin
Growth Factors/Receptors/Cytokines
Intracellular Signaling Molecules
Lymphoid Tissue Defects
Neurobiology Research
lacZ expression in neural tissue
Research Tools
lacZ Expression
Genetics Research
Tissue/Cell Markers
Tissue/Cell Markers: multiple
Tissue/Cell Markers: neurons
Immunology and Inflammation Research
genes regulating susceptibility to infectious disease and endotoxin
Neurobiology Research
cell marker
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Usp18tm1Dez | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Dong-Er Zhang | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | UBP43-; Usp18tm1Dzh; | ||
| Mutation Made By | Dong-Er Zhang, University of California, San Diego | ||
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| ES Cell Line Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| Site of Expression | Expression of lacZ is observed in brain tissues (expression in the ependymal cells of both the aqueduct and the ventricle). | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Molecular Note | Exons 2-4, which contain the translation initiation codon and Cys domain, were replaced with a neo-lacZ cassette via homologous recombination. Absence of gene expression in homozygous mutant animals was verified by Western blot analysis of LPS-stimulatedthymus glands. [MGI Ref ID J:78821] | ||
| Gene Symbol and Name | Usp18, ubiquitin specific peptidase 18 | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | 1110058H21Rik; AW047653; ISG43; RIKEN cDNA 1110058H21 gene; UBP43; expressed sequence AW047653; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Usp18tm1Dzh, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Malakhova OA; Kim KI; Luo JK; Zou W; Kumar KG; Fuchs SY; Shuai K; Zhang DE. 2006. UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity. EMBO J 25(11):2358-67. [PubMed: 16710296] [MGI Ref ID J:109574]
Ritchie KJ; Malakhov MP; Hetherington CJ; Zhou L; Little MT; Malakhova OA; Sipe JC; Orkin SH; Zhang DE. 2002. Dysregulation of protein modification by ISG15 results in brain cell injury. Genes Dev 16(17):2207-12. [PubMed: 12208842] [MGI Ref ID J:78821]
Additional References
Usp18tm1Dez relatedCong XL; Lo MC; Reuter BA; Yan M; Fan JB; Zhang DE. 2012. Usp18 promotes conventional CD11b+ dendritic cell development. J Immunol 188(10):4776-81. [PubMed: 22491252] [MGI Ref ID J:188680]
Giannakopoulos NV; Luo JK; Papov V; Zou W; Lenschow DJ; Jacobs BS; Borden EC; Li J; Virgin HW; Zhang DE. 2005. Proteomic identification of proteins conjugated to ISG15 in mouse and human cells. Biochem Biophys Res Commun 336(2):496-506. [PubMed: 16139798] [MGI Ref ID J:100999]
Kim KI; Malakhova OA; Hoebe K; Yan M; Beutler B; Zhang DE. 2005. Enhanced antibacterial potential in UBP43-deficient mice against Salmonella typhimurium infection by up-regulating type I IFN signaling. J Immunol 175(2):847-54. [PubMed: 16002682] [MGI Ref ID J:100695]
Kim KI; Yan M; Malakhova O; Luo JK; Shen MF; Zou W; de la Torre JC; Zhang DE. 2006. Ube1L and protein ISGylation are not essential for alpha/beta interferon signaling. Mol Cell Biol 26(2):472-9. [PubMed: 16382139] [MGI Ref ID J:144149]
Knobeloch KP; Utermohlen O; Kisser A; Prinz M; Horak I. 2005. Reexamination of the role of ubiquitin-like modifier ISG15 in the phenotype of UBP43-deficient mice. Mol Cell Biol 25(24):11030-4. [PubMed: 16314524] [MGI Ref ID J:103758]
Lopez R; Demick KP; Mansfield JM; Paulnock DM. 2008. Type I IFNs play a role in early resistance, but subsequent susceptibility, to the African trypanosomes. J Immunol 181(7):4908-17. [PubMed: 18802094] [MGI Ref ID J:142740]
Malakhova OA; Yan M; Malakhov MP; Yuan Y; Ritchie KJ; Kim KI; Peterson LF; Shuai K; Zhang DE. 2003. Protein ISGylation modulates the JAK-STAT signaling pathway. Genes Dev 17(4):455-60. [PubMed: 12600939] [MGI Ref ID J:119425]
Rempel LA; Austin KJ; Ritchie KJ; Yan M; Shen M; Zhang DE; Henkes LE; Hansen TR. 2007. Ubp43 gene expression is required for normal Isg15 expression and fetal development. Reprod Biol Endocrinol 5:13. [PubMed: 17381847] [MGI Ref ID J:121928]
Richer E; Prendergast C; Zhang DE; Qureshi ST; Vidal SM; Malo D. 2010. N-ethyl-N-nitrosourea-induced mutation in ubiquitin-specific peptidase 18 causes hyperactivation of IFN-alphabeta signaling and suppresses STAT4-induced IFN-gamma production, resulting in increased susceptibility to Salmonella Typhimurium. J Immunol 185(6):3593-601. [PubMed: 20693420] [MGI Ref ID J:163843]
Sarasin-Filipowicz M; Wang X; Yan M; Duong FH; Poli V; Hilton DJ; Zhang DE; Heim MH. 2009. Alpha interferon induces long-lasting refractoriness of JAK-STAT signaling in the mouse liver through induction of USP18/UBP43. Mol Cell Biol 29(17):4841-51. [PubMed: 19564419] [MGI Ref ID J:152613]
Yim HY; Yang Y; Lim JS; Lee MS; Zhang DE; Kim KI. 2012. The mitochondrial pathway and reactive oxygen species are critical contributors to interferon-alpha/beta-mediated apoptosis in Ubp43-deficient hematopoietic cells. Biochem Biophys Res Commun 423(2):436-40. [PubMed: 22683641] [MGI Ref ID J:185351]
Zou W; Kim JH; Handidu A; Li X; Kim KI; Yan M; Li J; Zhang DE. 2007. Microarray analysis reveals that Type I interferon strongly increases the expression of immune-response related genes in Ubp43 (Usp18) deficient macrophages. Biochem Biophys Res Commun 356(1):193-9. [PubMed: 17349616] [MGI Ref ID J:121441]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred. The donating investigator reports that homozygous mice on the FVB/N genetic background exhibit none of the severe neurologic disorders that lead to the perinatal lethality observed in homozygotes on a C57BL/6 or mixed B6;129 genetic backgoround.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2574.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|
|
|
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Payment Terms and Conditions
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
See Terms of Use tab for General Terms and Conditions
The Jackson Laboratory's Genotype Promise
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form
Terms of Use
Terms of Use
General Terms and Conditions
For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
Contact information
General inquiries regarding Terms of UseContracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.
No Liability
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.